Plain English Summary

Background and study aimsThe study is trying to find out whether a steroid drug called dexamethasone can help patients hospitalised with flu during a pandemic. Flu pandemics occur when a new flu virus emerges meaning that very few people have any protection against the virus. The new virus can therefore spread easily and cause serious illness. During a pandemic it is expected that many millions of people around the world will become ill. Some studies have shown that a steroid drug called dexamethasone helps people with pneumonia or severe 'blood poisoning' and we think that it may also help patients with pandemic flu but we are not sure. We are therefore trying to find out whether this treatment, given in addition to the normal flu treatment, will help adults who are admitted to hospital with pandemic flu to recover.

Who can participate? Adults (aged 16 years and above) who are admitted to hospital with flu-like symptoms during a pandemic will be asked to take part in the study. We are aiming to recruit 2200 patients.

What does the study involve?Patients will be randomly allocated to receive either dexamethasone or placebo (a 'dummy' treatment which looks like the real medicine but contains no active ingredient). Patients who take part will be given study medication to take once a day for 5 days. Using a placebo helps us to make a fair comparison of the treatment. The study medication will be given by mouth. For patients that are too poorly to take medication by mouth, the doctor may use a feeding tube to give medicines directly into the stomach. The study medication can be given in the same way. As well as the study medication, all patients will also receive the usual treatment given to patients with a flu-like illness.

What are the possible benefits and risks of participating? Steroids are very commonly used drugs. Side effects can include increased appetite, acne, mood changes, such as feeling very happy one minute and then very sad and weepy the next. Mood changes are very rare. Scientific studies of steroids in pneumonia and 'blood poisoning' have not found any major harmful effects from steroids. Less reliable studies have shown mixed results - some showed that patients who received steroids in the 2009 flu pandemic were less likely to die, other studies showed patients were more likely to die and yet others studies showed patients were not more likely to die, compared to patients who did not receive steroids. We cannot promise that the treatment will help, but the information that we get from the study might help improve the treatment of patients with pandemic flu in the second and third pandemic waves. This information should be applicable to patients around the world.

Where is the study run from? The study will take place in several hospitals throughout the United Kingdom. However we will only know which hospitals will be involved for certain once we know which areas are most affected by the pandemic. The study is being co-ordinated by the Nottingham Clinical Trials Unit.

When is the study starting and how long is it expected to run for? Once all approvals have been obtained the study will be placed in 'hibernation' until the study is activated during a flu pandemic.

Who is funding the study?National Institute for Health Research (NIHR) (UK)

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Study information

Scientific title

Early low-dose steroids for adults admitted to hospital with influenza-like illness during a pandemic: a randomised placebo controlled trial

Acronym

ASAP

Study hypothesis

During a pandemic, influenza infection can be severe because the population has little or no immune protection to the new virus. In such circumstances, severe influenza may lead to hospitalisation, admission to intensive care or death. A pandemic also poses challenges for health care systems which may be overstretched leading to further detrimental impacts on patient care. Current treatment options for influenza, including antivirals, are only partly effective at reducing adverse outcomes. Clinical trials of corticosteroids in patients with pneumonia or severe 'blood poisoning' have reported improved outcomes. There is uncertainty whether corticosteroids might also improve the recovery of patients with severe influenza infection. The ASAP trial will investigate whether low-dose corticosteroids (dexamethasone 6 mg once a day for 5 days) given to adults (aged 16 years and over) within 24 hours of admission to hospital with an influenza-like illness in addition to standard treatment are beneficial.

The influenza pandemics of the last century have typically spread in 2 or more waves, each wave approximately of 6 weeks duration. Therefore, we aim to complete recruitment (2200 patients) within a 6 week period corresponding to the first pandemic wave in order to inform pandemic management before the subsequent waves strike.

Condition

Intervention

Dexamethasone vs placebo, Participants will be randomised to receive either dexamethasone 6mg once daily for 5 days or placebo once daily for 5 days.

The planned sample size of 2200 patients is based on a high-severity pandemic along a range of possible scenarios. The outcome measures described relate to a high-severity pandemic, however the full statistical analyasis plan includes the flexibility to alllow for pandemics of different severity.

Intervention type

Drug

Phase

Phase III

Drug names

Dexamethsaone

Primary outcome measures

Admission to intensive care unit or death, within 30 days of admission to hospital

Secondary outcome measures

1. Admission to intensive care unit within 30 days of admission to hospital2. Death within 30 days of admission to hospital3. GP consultations within 30 days of hospital discharge4. Length of stay in hopsital5. Length of stay in intensive care unit6. Readmission to hospital within 30 days of hospital discharge

Overall trial start date

01/08/2013

Overall trial end date

01/05/2025

Reason abandoned

Eligibility

Participant inclusion criteria

This trial will be activated in the event of a pandemic. Trial activation will be decided by the NIHR in close discussion with the Trial Steering Committee, the Chief Investigators of the eight NIHR Pandemic Portfolio studies and the Department of Health. The following inclusion criteria will apply when the trial is activated:During an influenza pandemic, patients are eligible for the entry into the trial if they:1. Are aged ≥ 16 years2. Have been admitted to hospital within the previous 24 hours with a clinical diagnosis of an influenza-like illness 3. Have given consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 2200

Participant exclusion criteria

Patients are not eligible for the study if ANY of the following apply at the time of admission to hospital:1. Known to be taking oral or intravenous corticosteroid treatment2. Require treatment with oral or intravenous corticosteroids upon admission to hospital as standard treatment for comorbid illness.3. Known to be on insulin or oral medication for the treatment of diabetes mellitus4. Known contra-indication to dexamethasone or any of the excipients

Intention to publish date

Participant level data

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

01/12/2016: Please note that this trial has not yet started. The trial is currently set up and being maintained in a state of readiness, so that patients can participate in the trial from the start of the next flu pandemic.